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Prospective analysis of vitamin D and endometrial cancer risk.

ABSTRACT: BACKGROUND:This is the first prospective cohort analysis on the association between vitamin D and endometrial cancer incorporating time-varying predicted plasma 25-hydroxyvitamin D [25(OH)D]. METHODS:The prospective cohort analysis of predicted 25(OH)D and total dietary vitamin D intake used the Cox proportional hazards model, and involved 644 incident endometrial cancer events from 1986 to 2006 in the Nurses' Health Study. Genotyping and unconditional logistic regression were carried out on 572 endometrial cancer cases and their matched controls on 12 single nucleotide polymorphisms (SNPs) in vitamin D-related genes. RESULTS:There was no significant association between predicted 25(OH)D and endometrial cancer incidence, with the hazard ratio for the highest (versus the lowest) quintile of predicted 25(OH)D as 1.00 (95% CI 0.73-1.36) (p-trend = 0.33). There was also no significant association involving total dietary vitamin D. No significant associations between any of the vitamin D-related SNPs and endometrial cancer were observed. CONCLUSION:Both predicted 25(OH)D and total dietary vitamin D intake were not associated with endometrial cancer incidence. These results suggest that vitamin D may not protect against the development of endometrial cancer. However, the low and narrow vitamin D exposure range in the cohort may limit generalizability of the results.

SUBMITTER: Liu JJ

PROVIDER: S-EPMC3574547 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Prospective analysis of vitamin D and endometrial cancer risk.

Liu J J JJ Bertrand K A KA Karageorgi S S Giovannucci E E Hankinson S E SE Rosner B B Maxwell L L Rodriguez G G De Vivo I I

Annals of oncology : official journal of the European Society for Medical Oncology 20121107 3

<h4>Background</h4>This is the first prospective cohort analysis on the association between vitamin D and endometrial cancer incorporating time-varying predicted plasma 25-hydroxyvitamin D [25(OH)D].<h4>Methods</h4>The prospective cohort analysis of predicted 25(OH)D and total dietary vitamin D intake used the Cox proportional hazards model, and involved 644 incident endometrial cancer events from 1986 to 2006 in the Nurses' Health Study. Genotyping and unconditional logistic regression were car ...[more]

PMID: 23136228

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Project description:BackgroundObservational studies indicated that circulating vitamin C (VitC) levels may be correlated with the risk of endometrial cancer (EC). However, the causal effects and direction between them were still unclear.MethodsIn this study, 11 single nucleotide polymorphisms (SNPs) robustly correlated with plasma VitC levels were extracted from the latest genome-wide association study (GWAS), containing 52,018 individuals. Genetic data of EC were obtained from the Endometrial Cancer Association Consortium (ECAC) (12,906 cases and 108,979 controls). An inverse-variance weighted method was utilized as the primary analysis of Mendelian randomization (MR), supplemented by the weighted median, MR Pleiotropy Residual Sum and Outlier test (MR-PRESSO), and MR-Egger methods. Additional sensitivity analyses excluding 3 SNPs with secondary phenotypes were conducted to rule out the possible pleiotropic effects. Potential impacts of several risk factors of EC, such as obesity, body mass index (BMI), hypertension, and diabetes on VitC levels, were assessed. We additionally evaluated the effects of VitC on LDL cholesterol levels, HDL cholesterol levels, and triglycerides levels to probe into the possible mediators in the VitC-EC pathway.ResultsGenetically predicted higher plasma VitC levels (per 1 SD increase, approximately 20 μmol/L) were causally associated with an increased risk of EC overall [odds ratio (OR) 1.374, 95% CI 1.128-1.674, p = 0.0016], supported by complementary sensitivity analyses. In the subgroup analyses, genetically predicted higher levels of VitC were associated with a tendency of increased risks of both endometrioid (OR SD 1.324, 95% CI 0.959-1.829, p = 0.0881) and non-endometrioid histology (OR SD 1.392, 95% CI 0.873-2.220, p = 0.1647) while without statistical significance. The association remained significant after the exclusion of the three pleiotropic SNPs (OR SD 1.394, 95% CI 1.090-1.784, p = 0.0082). The confounders and mediators were unlikely to affect the VitC-EC relationship. The causal effect of EC on VitC levels was not supported (OR 1.001, 95% CI 0.998-1.004, p = 0.4468).ConclusionsThis bi-directional MR study demonstrated a causal risk role of higher circulating VitC at physiological levels on an increased risk of EC, which was independent of confounders and mediators. Further studies are warranted to elucidate the possible mechanisms.

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Prospective analysis of vitamin D and endometrial cancer risk.

Publications

Prospective analysis of vitamin D and endometrial cancer risk.

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